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PubMed1993

Comparison of five histopathologic methods to assess cellular proliferation in transitional cell carcinoma of the urinary bladder.

Transitional cell carcinomas of the urinary bladder vary in their biologic potential, which may be correlated with the grade and stage of the tumor. Cellular proliferation may prove to be another measure of predicting tumor biologic potential. We have compared five different methods to assess proliferation in 26 tumors and correlated these results with tumor grade and stage. A portion of each tumor was incubated in vitro with bromodeoxyuridine (BrdUrd). For each tumor this was compared with at least three of the following four other markers of proliferation: mitotic count, silver-stained nucleolar organizer regions, immunohistochemical staining with Ki67, and proliferating cell nuclear antigen. Statistical correlations were seen between tumor grade and stage and these markers. There were strong correlations between the BrdUrd labeling index (LI) and both the Ki67 LI and proliferating cell nuclear antigen LI. The correlation between the BrdUrd LI and mitotic count was more tenuous; no significant correlation was found between BrdUrd LI and silver-stained nucleolar organizer region count. The correlation between these measurements of proliferation and tumor grade and stage was less strong. Our data suggest that cellular proliferation of transitional cell carcinomas can be reliably assessed with several different markers and that most of these markers can be correlated with tumor grade but not with stage.

Bromodeoxyuridine↗

PubMed1982

Active and passive Na+ fluxes across the basolateral membrane of rabbit urinary bladder.

The apical membrane of rabbit urinary bladder can be functionally removed by application of nystatin at high concentration if the mucosal surface of the tissue is bathed in a saline which mimics intracellular ion concentrations. Under these conditions, the tissue is as far as the movement of univalent ions no more than a sheet of basolateral membrane with some tight junctional membrane in parallel. In this manner the Na+ concentration at the inner surface of the basolateral membrane can be varied by altering the concentration in the mucosal bulk solution. When this was done both mucosal-to-serosal 22Na flux and net change in basolateral current were measured. The flux and the current could be further divided into the components of each that were either blocked by ouabain or insensitive to ouabain. Ouabain-insensitive mucosal-to-serosal Na+ flux was a linear function of mucosal Na+ concentration. Ouabain-sensitive Na+ flux and ouabain-sensitive, Na+-induced current both display a saturating relationship which cannot be accounted for by the presence of unstirred layers. If the interaction of Na+ with the basolateral transport process is assumed to involve the interaction of some number of Na+ ions, n, with a maximal flux, MMAX, then the data can be fit by assuming 3.2 equivalent sites for interaction and a value for MMAX of 287.8 pM cm-2 sec-1 with an intracellular Na concentration of 2.0 mM Na+ at half-maximal saturation. By comparing these values with the ouabain-sensitive, Na+-induced current, we calculate a Na+ to K+ coupling ratio of 1.40 +/- 0.07 for the transport process.

Animals↗

PubMed1993

Role of calcium in mediating the biphasic contraction of the rabbit urinary bladder.

1. The response of the urinary bladder to field stimulation is biphasic in nature consisting of an initial phasic contraction followed by a prolonged tonic phase which lasts for the duration of the stimulation. 2. The phasic response is mediated by the release of neurohumoral transmitters, primarily acetylcholine (via muscarinic receptor stimulation) and ATP (via purinergic receptor stimulation). The tonic component is mediated entirely via muscarinic receptor stimulation. 3. The present study investigates the dependence on extracellular calcium of the phasic and tonic contractile responses to field stimulation, bethanechol, and ATP. The results can be summarized as follows: 4. Field stimulation (2 and 32 Hz) and bethanechol evoke a biphasic contractile response whereas ATP evokes only a phasic response. 5. There were no significant effects of either calcium channel blockers or calcium fee EGTA medium on either spontaneous contraction or basal tension of muscle strips. 6. The calcium channel antagonists diltiazem and verapamil inhibited both the phasic and tonic responses induced by field stimulation (both 2 and 32 Hz) in a dose dependent manner. 7. For both 2 and 32 Hz stimulation, the ED50 s for the inhibition of the tonic phases of the responses to field stimulation were significantly lower than the ED50s for the inhibition of the phasic responses. 8. The tonic phase of the responses to field stimulation were inhibited to a significantly greater degree than the phasic responses by incubation in calcium-free medium containing EGTA. 9. Both the phasic and tonic components of the response to bethanechol stimulation were inhibited equally, and followed a similar time course as the tonic component of field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1995

cAMP accelerates the decay of stretch-activated inward currents in guinea-pig urinary bladder myocytes.

1. Myocytes from the urinary bladder were stretched longitudinally by 5-20%. At -50 mV, stretch induced whole-cell inward currents (Iin) between -100 and -600 pA. Iin decayed slowly with time to 93 +/- 20% (mean +/- S.E.M., n = 6) of the initial value in 1 min. The mechanisms of this 'adaptation' and its modulation by dibutyryl cAMP (dBcAMP) were analysed with whole-cell and single channel currents. 2. When the cells were internally perfused with 100 microM 8-bromo-cAMP (8BrcAMP), stretch induced an Iin of the usual amplitude that decayed completely within 40 +/- 13 s. When 200 microM dBcAMP was bath applied 10 s after the start of the stretch, Iin decayed to zero within 85 +/- 18 s. 3. dBcAMP increased the K+ current through Ca(2+)-activated BK channels (IK(Ca)) at 0 mV with a time course that correlated well with the decay of Iin, and block of IK(Ca) by TEA suppressed the dBcAMP-induced decay of Iin. In the presence of intracellular BAPTA, dBcAMP increased the stretch-induced Iin. The results suggest that adaptation is caused by superimposition of IK(Ca) which is increased through elevation of near-membrane [Ca2+] and by cAMP-dependent phosphorylation. 4. Single channel analysis was carried out with 140 mM KCl electrode solution and at -50 mV. Stretch-activated channels (SACs) were recorded during pulses of negative pressures between -2 and -5 kPa. Activity (NPo) of SACs was constant for at least 4 min, e.g. evidence for adaptation was missing. dBcAMP (200 microM) increased NPo of SACs by 142 +/- 35% (n = 16). 5. dBcAMP increased NPo via frequency of openings and channel open time. In five of sixteen patches, dBcAMP induced openings without suction. Similar effects were induced by the catalytic subunit of cAMP-dependent protein kinase (PKAc), applied to inside-out patches. 6. NPo, normalized by its maximum, increased with more negative pressure along an S-shaped curve. dBcAMP increased the sensitivity of SACs to stretch by shifting the point of half-maximal activity from -3.2 to -2.6 kPa. 7. The augmentation of NPo by dBcAMP is attributed to the phosphorylation of SACs promoting their opening. Adaptation of Iin is discussed as a 'secondary' effect of stretch-activated channels: Ca2+ influx through SACs increases the Ca2+ concentration that activates BK channels whose Ca2+ sensitivity is increased by cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1989

[Urinary bladder carcinogenicity of BBN in beige mice (Chediak-Higashi disease model)].

To study the effect of natural killer (NK) activity on chemical carcinogenesis in urinary bladder cancer, beige mice (NK deficient mice) and C57BL/6 mice (NK normal mice) received N-bytyl-(4-hydroxybutyl) nitrosamine (BBN) in drinking-water. The effect was evaluated by measuring the incidence of early neoplastic change in the urinary bladder. OK-432, a biological response modifier, was administered in drinking-water and its effect on carcinogenesis was evaluated. The beige and C57BL/6 mice were divided into two groups. Group A, C57BL/6 mice and group C, beige mice received 0.1% BBN in their drinking-water. Group B, C57BL/6 mice, and group D, beige mice, received 0.1% BBN and OK-432 (5KE/1000 ml) in their drinking-water for 4 weeks. The mice were sacrificed at 12, 14, 16, 18 and 24 weeks after BBN administration and the urinary bladder was examined histologically by light and scanning electron microscopy. In the light microscopic findings, all groups had no neoplastic change at 12, 14 and 16 weeks, although at 18 and 24 weeks, neoplastic changes were observed. The incidence at 18 weeks was 0/10 in in group B, 2/5 in group C and 3/6 in group D. (p less than 0.01 between beige and C57BL/6 mice at 18 weeks). In the scanning electron microscopic findings, cells with a cobble stone appearance, pleomorphic microvilli and short uniform microvilli on luminal surfaces are observed during carcinogenesis in urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1975

Inverted papillomas of the urinary bladder.

Study of 20 patients with inverted papilloma of the urinary bladder and urethra revealed that the lesion is a true neoplasm, benign in its histologic morphology and clinical behavior. The lesion is believed to arise from the trigone and bladder outlet as a result of chronic proliferative cystitis. It occurs predominantly in men who are past middle age. The most commonly associated clinical symptoms are hematuria and those of urinary obstruction. The lesion may be easily mistaken for a low-grade papillary transitional cell carcinoma, although the histologic appearance is distinctly different, as is its subsequent behavior.

Adult↗

PubMed2000

[Primary paraganglioma of the urinary bladder with high serum CA19-9 level: a case report].

A case of primary paraganglioma of the urinary bladder with a high serum CA19-9 level is reported. A 44-year-old woman visited our hospital with the chief complaint of lower abdominal pain. Magnetic resonance imaging (MRI) examination incidentally revealed a cystic bladder tumor. Cystoscopy disclosed a broad-based non-papillary tumor on the posterior wall of the urinary bladder. With the diagnosis of a bladder submucosal cystic tumor transurethral needle puncture and biopsy were performed. The solution sampled with puncture was bloody. The patient suddenly complained of headache and blood pressure was elevated to 215/120 mmHg when we held the tumor with a cold cup biopsy forceps. Catecholamine levels of the solution in the tumor were abnormally elevated. The serum CA19-9 level was also raised. Ten days later, she underwent partial cystectomy. Histological findings of the removed specimen showed primary paraganglioma of the urinary bladder. The serum CA19-9 level decreased to normal limits on the 28th postoperative day. Our experience suggests that the level of serum CA19-9 may serve as a useful index for observing the clinical course of a patient with this disease.

Adult↗

PubMed2002

[Multiple synchronous primary malignant tumors of fibrosarcoma and squamous cell carcinoma in the urinary bladder: a case report].

A 65-year-old housewife presented with a diagnosis of malignant spindle cell tumor of the bladder which had been diagnosed by work up for chance hematuria. Urine cytology revealed a small number of squamous epithelial cells showing dyskeratosis but no spindle cells. Computed tomography and magnetic resonance images showed a markedly enhanced mass, 4 cm in diameter, on the anterior wall of the urinary bladder, which appeared to be adhesive to the pubic bone. However, no metastasis was found. Under the suspicion of sarcoma of the urinary bladder, we performed anterior pelvic exenteration with construction of an ileal conduit. Although the anterior wall of the urinary bladder was mildly adhesive to the pubic bone, the surgical margin was negative for malignant cells. The tumor corresponded to a fibrosarcoma that infiltrated the adipose tissue surrounding the urinary bladder. The entire mucosa of the bladder showed diffuse squamous metaplasia, and well differentiated squamous cell carcinoma with pearl formation was found in part. These two malignant tumors were clearly apart from each other, resulting in the histologic diagnosis of synchronous multiple malignant tumors of the bladder. The patient developed a local relapse and pulmonary metastasis of fibrosarcoma one month postoperatively and died two month later without any response to chemotherapy (CYVADIC) and radiotherapy. The current case seems to be the first one in Japan (third in the world) of a patient with multiple synchronous primary malignant tumors, carcinoma and sarcoma, airsing in the urinary bladder.

Aged↗

PubMed1981

Carcinogenesis in heterotopically-transplanted urinary bladder by N-methyl-N-nitrosourea: a model for initiation and promotion.

The present investigation was conducted to establish a working model to evaluate the role of potential modifiers (promoters and inhibitors) of urinary bladder carcinogenesis. A single dose (0.25 mg) of the carcinogen N-methyl-N-nitrosourea (MNU) when instilled directly into heterotopically transplanted urinary bladder (HTB) induced a 9% (2 of 22) incidence of urinary bladder tumors by 30 weeks in the urine free HTB environment, whereas repeated instillation of urine into the HTB after MNU treatment resulted in a 61% (14 of 23) incidence of these tumors. Three doses of MNU (0.25 mg/dose once a week for 3 weeks) induced 33% (6 of 18) and 89% (16 of 18) incidence of tumors, respectively, in the absence and presence of urine in the HTB. These data confirm our previous observation that normal urine enhances urinary bladder carcinogenesis, and are consistent with the notion that normal urine exerts a tumor promoting effect.

Animals↗

PubMed1975

Further observations on carcinoma in situ of the urinary bladder: silent but extensive intraprostatic involvement.

Of seven patients with carcinoma in situ of the urinary bladder in the absence of an associated papillary carcinoma, five were found to have silent but extensive intraductal prostatic involvement. In three of these the carcinoma in situ was associated with microinvasion. The mean age at the time of diagnosis was 68 years. All had symptoms characteristic of carcinoma in situ, including hematuria, dysuria, and urgency. In three patients the prostatic involvement was diagnosed on transurethral resection. In two it was discovered only after radical cystectomy. The prostatic involvement was neither suspected clinically nor has it been previously emphasized. Although three patients are alive, apparently free of disease up to 15 months postcystectomy, two have died, one of disease. The importance of prostatic assessment in the evaluation of the patient with carcinoma in situ of the urinary bladder is emphasized.

Aged↗

PubMed2003

Transitional cell carcinoma of the urinary bladder metastatic to the orbit.

We report a rare case of transitional cell carcinoma of the urinary bladder metastatic to the orbit, review the histopathology, and highlight characteristics of the few previously reported cases. A 68-year-old man with a remote history of transitional cell carcinoma of the urinary bladder presented with decreased visual acuity, afferent pupillary defect, and limited extraocular motility OS. Computed tomography scan of the orbits showed a diffuse infiltrate surrounding the left globe and optic nerve. Biopsy revealed metastatic transitional cell carcinoma. The patient expired one month later. With only seven cases previously reported, we conclude that transitional cell carcinoma of the urinary bladder rarely metastasizes to the orbit. When present, orbital metastases signify aggressive disease and a poor prognosis. Mean survival following orbital diagnosis is 2.2 months in the cases reported.

Aged↗

PubMed1999

Enhancement of urinary bladder carcinogenesis in nullizygous p53-deficient mice by N-butyl-N-(4-hydroxybutyl)nitrosamine.

We recently reported p53 mutations to be frequent in mouse invasive urinary bladder carcinomas, with and without metastasis. However, the role of p53 dysfunctions during carcinogenesis remains unclear. In the present study, heterozygous and nullizygous p53-deficient mice and their littermates were treated with the urinary bladder carcinogen, N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), at a concentration of 0.01% in the drinking water throughout the experiment. This markedly accelerated urinary bladder carcinogenesis but not development of other tumors in the nullizygous p53-deficient mice. Thus the appearance of neoplastic urothelial lesions in nullizygotes (at day 60 of the experiment) was earlier than in wild-type mice and heterozygotes (at day 125). Moreover, malignant vascular tumors (hemangiosarcomas (HS)) were found in all four nullizygotes killed later than day 108. Mutational inactivation of the wild-type allele was not apparent in either the single transitional cell carcinoma observed in a wild-type mouse and a hemangiosarcoma in a heterozygote. Overall, it can be concluded that the number of normal p53 alleles is a significant determining factor in the susceptibility of urothelial cells to carcinogens. The role of the p53 defect in mouse urinary bladder carcinogenesis may thus be to diminish the threshold for occurrence of additional genetic alterations.

Animals↗

PubMed2001

Pharmacological characterization of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle.

1. The pharmacological characteristics of muscarinic receptors mediating contraction of dog isolated ciliary muscle were determined and compared to those mediating contraction of dog urinary bladder smooth muscle. 2. (+)-Cis-dioxolane induced concentration-dependent contractions of ciliary muscle (pEC50=7.18+/-0.07, Emax=453+/-64 mg, n=19) and urinary bladder isolated smooth muscle (pEC50=6.55+/-0.07, Emax=11+/-1 g, n=19). These responses were antagonized by several muscarinic receptor antagonists (pKb values for the ciliary muscle and the bladder smooth muscle, respectively): atropine (8.25+/-0.14 and 9.21+/-0.09), pirenzepine (6.31+/-0.13 and 6.70+/-0.25), tolterodine (7.97+/-0.14 and 8.68+/-0.12), oxybutynin (7.40+/-0.08 and 7.88+/-0.12), zamifenacin (6.46+/-0.19 and 7.69+/-0.11), S-secoverine (6.66+/-0.14 and 8.13+/-0.07), AQ-RA 741 (6.16+/-0.15 and 7.08+/-0.23), p-F-HHSiD (7.10+/-0.27 and 7.35+/-0.07) and responses were not antagonized by PD 102807 (up to 100 nM). 3. In urinary bladder smooth muscle, the profile of antagonist pKB values correlated significantly with pK(i) values at human recombinant m3 muscarinic receptors, suggesting that M3 muscarinic receptors mediated the response. In the ciliary muscle, a significant (P<0.01) correlation was obtained with human recombinant m3 and m5 receptors. 4. Darifenacin displayed insurmountable antagonism at receptors in the bladder. At receptors in the ciliary muscle, it exhibited two phases of antagonism, comprising an initial low affinity (pKB<6) component and a high affinity phase (pKB>8). 5. The role of pigmentation in the atypical behaviour of darifenacin was examined. In blue coloured eyes, darifenacin produced apparent surmountable, competitive antagonism of the responses to (+)-cis-dioxolane (pKB=8.76+/-0.07). The antagonist profile obtained in this tissue suggested the involvement of a site which has the pharmacological attributes of the M5 receptor. 6. We suggest that the dog urinary bladder contracts in response to M3 muscarinic receptor activation. Contraction of the brown-eyed dog ciliary muscle is more complex and may include involvement of at least two receptors, possibly the M5 and M3 receptor, whereas blue-eyed dog ciliary muscle may involve a single population of M5 muscarinic receptors.

Animals↗

PubMed1988

Effects of urinary crystals induced by acetazolamide, uracil, and diethylene glycol on urinary bladder carcinogenesis in N-butyl-N-(4-hydroxybutyl)nitrosamine-initiated rats.

In order to examine the promoting effect of urinary crystals on urinary bladder carcinogenesis, acetazolamide, uracil, and diethylene glycol, all of which have been reported to cause urinary crystals or calculi, were administered to male F344 rats for 32 weeks after pretreatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks. A marked increase in urinary crystals was observed in acetazolamide-treated rats and a slight increase in crystals was observed in uracil- and diethylene glycol-treated rats. Histological examination of the urinary bladder revealed that the BBN-acetazolamide treatment resulted in a higher incidence of carcinoma than BBN-control. Uracil and diethylene glycol did not cause any significant difference compared to the control. Promoting effects by urinary crystals were not clearly shown in the present experiment and, therefore, urinary crystals appear to play a very limited role, if any, in urinary bladder carcinogenesis.

Acetazolamide↗

PubMed1974

Lymphoid cells mediating tumor-specific cytotoxicity to carcinoma of the urinary bladder. Separation of the effector population using a surface marker.

Peripheral lymphocytes from patients with urinary bladder carcinoma and controls have been separated on the basis of rosette formation with sheep erythrocytes. The fractions were tested for tumor-specific cytotoxicity. The E rosette-forming cells of purity 90% respond well in PHA-induced cytotoxicity but are totally inactive in the tumor assay. The non-E rosette-forming cells (purity 91%) give enhanced activity in the tumor-specific cytotoxicity as well as in antibody-mediated target cell lysis in a model system. These data support the notion that the effector cells in cell-mediated immunity to carcinoma of the urinary bladder are members of the nonthymus-derived population of peripheral lymphocytes.

B-Lymphocytes↗

PubMed1980

Induction of a transplantable urinary bladder carcinoma in dogs.

We attempted to reduce the carcinoma induction latency period and to produce a transplantable urinary bladder cancer in dogs. After transurethral pellet application, 12 of 22 female beagles were given subcutaneous injections of orthoaminodiphenyl, FANFT, or both. Monthly cytologic and histologic checks yielded the earliest evidence yet obtained for invasive urothelial urinary bladder carcinoma (15 months); seven urothelial carcinomas of the urinary bladder and three of the renal pelvis were established. Tissue cultures of the urothelial carcinomas in vitro were successful. Transplantation of tumor cells to 23 nude mice resulted in tumor growth in 19. Transplantation to 10 beagles yielded 2 tumors very quickly, but the tumors were rejected within 4 weeks.

Animals↗

PubMed1992

Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distension.

The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields; whereas, thoracic STT cells are inhibited by UBD. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P less than 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex.

Action Potentials↗

PubMed2006

[Isolated neurofibromatosis of the urinary bladder. A rare cause of recurrent cystitis].

Neurofibromas of the urinary bladder occur as isolated phenomena or as part of generalized neurofibromatosis or von Recklinghausen's disease. This benign mesenchymal tumor can be the cause of subvesical obstruction, hematuria or chronic cystitis. The lesion is rare. Our case of isolated extended neurofibromatosis of the urinary bladder was diagnosed in a 19-year-old girl with an 8-year history of chronic cystitis. Two transurethral resections were successful in relieving symptoms. Possible further therapy was delayed because of the patient's desire for children.

Adult↗